Jonathan Terman, Ph.D. Professor Endowed Title Rita C. and William P. Clements, Jr. Scholar in Medical Research School Medical School Department Neuroscience | Pharmacology Graduate Programs Neuroscience Biography Biosketch: Dr. Terman completed his Bachelor of Science degree in biology at Wheaton College in Wheaton, Illinois. After working for a year in Marine Science at the College of William and Mary’s Virginia Institute of Marine Science, he began his graduate work at Ohio State University and received his PhD in neuroscience. As a graduate student in George F. Martin’s laboratory, he utilized the unique embryology of the marsupial opossum and focused on understanding the potential for axon regeneration in the spinal cord of mammals and the factors associated with its failure. As an initial step towards identifying the molecular mechanisms limiting axon regeneration, Dr. Terman focused his postdoctoral training on investigating the molecular mechanisms that enable axonal growth and guidance. While a postdoctoral fellow with Alex L. Kolodkin at the Johns Hopkins University School of Medicine, Dr. Terman utilized molecular and genetic approaches in both Drosophila and mammals to better characterize the molecular mechanisms underlying axon guidance. He joined the faculty of UT Southwestern in 2005. Research: A normal functioning human nervous system requires the interconnection of billions of neurons but much remains to be learned on how these circuits are assembled, and how they may be repaired after injury or disease. Remarkably, the signals that help neurons find and connect with their targets appear common to all animals. Simple animals like worms and flies use many of the same axon guidance signals as more complex animals. These extracellular axon guidance signals or cues guide axons by associating with cell surface receptors present on growing axons. How these axon guidance cues alter the cytoskeletal machinery necessary to steer an axon is still poorly understood, however. Relatively little is known of the intracellular signaling molecules and mechanisms within the growing tip of an axon that orchestrate growth, navigation, and target selection. Research in my laboratory focuses on better understanding the molecules and mechanisms that assemble axonal connections with a goal of utilizing this knowledge to encourage axons to reestablish their connections after trauma or disease. To address these questions, we employ a combination of molecular, biochemical, structural, genetic, and cell biological approaches both in vivo and in vitro in simple and complex organisms. Work currently underway in the lab is focused on 1) identifying the molecules involved in neural connectivity and assembling them into signaling pathways, 2) studying the functional importance of these proteins in the formation of the nervous system, 3) characterizing the biochemical and physiological role of these proteins, and 4) using these findings to devise and test therapeutic strategies to encourage axons to regrow after injury. One of our major interests is to better characterize a new family of proteins, the MICALs, that contain a flavoprotein oxidoreductase domain that is required for proper neuronal connectivity. Our recent results reveal that MICALs are oxidoreductase enzymes that utilize novel oxidation-reduction (redox) signaling mechanisms to directly regulate the actin cytoskeletal elements necessary for axonal growth, steering, and targeting. This work reveals new mechanisms underlying neural connectivity and also identifies a new class of enzymes that regulate the actin cytoskeleton, the basic building blocks for many aspects of cell behavior. Education Undergraduate Wheaton College , Biology Graduate School Ohio State University-Main Cam (1997) Research Interest Actin Cytoskeleton Axonal Growth and Guidance Axonal Regeneration Cell Signaling and Motility in Normal and Cancerous Cells Neuronal Connectivity Publications Featured Publications Profilin and Mical combine to impair F-actin assembly and promote disassembly and remodeling. Grintsevich EE, Ahmed G, Ginosyan AA, Wu H, Rich SK, Reisler E, Terman JR, Nat Commun 2021 Sep 12 1 5542 Propagation of F-actin disassembly via Myosin15-Mical interactions. Rich SK, Baskar R, Terman JR, Sci Adv 2021 May 7 20 The MICALs are a Family of F-actin Dismantling Oxidoreductases Conserved from Drosophila to Humans. Wu H, Yesilyurt HG, Yoon J, Terman JR Sci Rep 2018 Jan 8 1 937 Catastrophic disassembly of actin filaments via Mical-mediated oxidation. Grintsevich EE, Ge P, Sawaya MR, Yesilyurt HG, Terman JR, Zhou ZH, Reisler E Nat Commun 2017 Dec 8 1 2183 Amplification of F-Actin Disassembly and Cellular Repulsion by Growth Factor Signaling. Yoon J, Kim SB, Ahmed G, Shay JW, Terman JR Dev. Cell 2017 Jul 42 2 117-129.e8 F-actin dismantling through a redox-driven synergy between Mical and cofilin. Grintsevich EE, Yesilyurt HG, Rich SK, Hung RJ, Terman JR, Reisler E Nat. Cell Biol. 2016 Aug 18 8 876-85 SelR reverses Mical-mediated oxidation of actin to regulate F-actin dynamics. Hung RJ, Spaeth CS, Yesilyurt HG, Terman JR Nat. Cell Biol. 2013 Nov 14-3-3e Couples Protein Kinase A to Semaphorin Signaling and Silences Plexin RasGAP-Mediated Axonal Repulsion. Yang T, Terman JR Neuron 2012 Apr 74 1 108-21 Direct Redox Regulation of F-Actin Assembly and Disassembly by Mical. Hung RJ, Pak CW, Terman JR Science 2011 Nov Mical links semaphorins to F-actin disassembly. Hung RJ, Yazdani U, Yoon J, Wu H, Yang T, Gupta N, Huang Z, van Berkel WJ, Terman JR Nature 2010 Feb 463 7282 823-7 Results 1-10 of 10 1 Books Featured Books Semaphorin Signaling (Ed.) (2017). New York, Humana Press, Springer Nature Honors & Awards Genetics Society of America Drosophila Image Award Finalisthttp://www.drosophila-images.org/2011.shtml (2011) Welch Foundation Research Grant (2009) Klingenstein Fellowship Award in the Neurosciences (2006) March of Dimes Basil O’Connor Starter Scholar Research Award (2006) Whitehall Foundation Research Award (2005) NIH Research Scientist Career Development Award (K01) (2003)